Diagnosis and treatment of upper-tract urothelial carcinomas (UTUC) remain very challenging for urologists. Standard management for many years has been radical nephroureterectomy (RNU). However, RNU is a significant over-treatment for low-risk tumors, which have low rate of progression. Endoscopic management of these low-risk cases bears obvious advantages over RNU, including lower co-morbidity and lower cost, and would be highly feasible if accurate diagnosis can be made. The success of endoscopic management relies on accurate identification of low-grade and low-stage tumors, but staging of UTUC is very difficult even through biopsy. Usually, adequate tissue specimens for pathohistological staging cannot be acquired because of the limited manipulation space in the ureter and renal pelvis and the potential risk of perforating thin ureteral wall if deep biopsyis attempted. Therefore, urologists typically make a diagnosis only based on the tumor grade, which is also inefficient because of the limitations of biopsy, and which, alone, is not sufficientto make certain treatment decisions. Therefore, if the stage of UTUC could be safely and reliably identified, urologists would have complete information for diagnosis, which could significantly improve endoscopic management of UTUC. We propose to stage UTUC through endoscopic optical coherence tomography (OCT). The feasibility of this in situ imaging approach is supported by the fact that OCT has already been shown to be able to stage bladder urothelial cancer, which is histologically similar to UTUC and uses the same staging system as UTUC. We have demonstrated that OCT can acquire high-quality images of the ureter through a probe ex vivo. In this project, we will implement OCT probes specifically for imaging of UTUC and test the safety and preliminary efficacy of staging of UTUC in a two-stage pilot study, including a training stage and a testing stage. Success of this project will result in: (a) an endoscopic OCT system designed and proven safe for UTUC imaging, (b) tested OCT image-based diagnostic criteria, and (c) a preliminary estimate of the accuracy of OCT staging of UTUC. This will justify and set the stage for larger scale clinical validation. PUBLIC HEALTH RELEVANCE: Endoscopic treatment of early-stage upper-tract urothelial cancer (UTUC) could be cheaper and better for the patient than radical surgery, which is the standard care, but it can't currently be reliably used because no technology is available to accurately stage UTUC. This project will validate use of endoscopic OCT imaging to stage UTUC safely and quickly.